Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30088 | 90487;90488;90489 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| N2AB | 28447 | 85564;85565;85566 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| N2A | 27520 | 82783;82784;82785 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| N2B | 21023 | 63292;63293;63294 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| Novex-1 | 21148 | 63667;63668;63669 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| Novex-2 | 21215 | 63868;63869;63870 | chr2:178552638;178552637;178552636 | chr2:179417365;179417364;179417363 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1238844529  |
None | 0.927 | N | 0.458 | 0.136 | 0.351830644314 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs1238844529 |
None | 0.927 | N | 0.458 | 0.136 | 0.351830644314 | gnomAD-4.0.0 | 6.57212E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46994E-05 | 0 | 0 |
| I/T | None | None | 0.425 | N | 0.419 | 0.226 | 0.456647468687 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1951 | likely_benign | 0.1803 | benign | -1.918 | Destabilizing | 0.3 | N | 0.433 | neutral | None | None | None | None | N |
| I/C | 0.6018 | likely_pathogenic | 0.589 | pathogenic | -1.448 | Destabilizing | 0.003 | N | 0.319 | neutral | None | None | None | None | N |
| I/D | 0.7979 | likely_pathogenic | 0.7668 | pathogenic | -1.008 | Destabilizing | 0.543 | D | 0.522 | neutral | None | None | None | None | N |
| I/E | 0.6326 | likely_pathogenic | 0.5987 | pathogenic | -0.889 | Destabilizing | 0.704 | D | 0.538 | neutral | None | None | None | None | N |
| I/F | 0.1185 | likely_benign | 0.1101 | benign | -1.087 | Destabilizing | 0.001 | N | 0.133 | neutral | N | 0.360634515 | None | None | N |
| I/G | 0.601 | likely_pathogenic | 0.5712 | pathogenic | -2.358 | Highly Destabilizing | 0.329 | N | 0.436 | neutral | None | None | None | None | N |
| I/H | 0.5293 | ambiguous | 0.4949 | ambiguous | -1.548 | Destabilizing | 0.944 | D | 0.583 | neutral | None | None | None | None | N |
| I/K | 0.4206 | ambiguous | 0.4057 | ambiguous | -1.196 | Destabilizing | 0.704 | D | 0.539 | neutral | None | None | None | None | N |
| I/L | 0.0981 | likely_benign | 0.0986 | benign | -0.723 | Destabilizing | 0.139 | N | 0.315 | neutral | N | 0.406174803 | None | None | N |
| I/M | 0.0541 | likely_benign | 0.0534 | benign | -0.81 | Destabilizing | 0.927 | D | 0.458 | neutral | N | 0.452795314 | None | None | N |
| I/N | 0.3863 | ambiguous | 0.3392 | benign | -1.2 | Destabilizing | 0.002 | N | 0.478 | neutral | N | 0.494065934 | None | None | N |
| I/P | 0.9476 | likely_pathogenic | 0.9333 | pathogenic | -1.093 | Destabilizing | 0.981 | D | 0.599 | neutral | None | None | None | None | N |
| I/Q | 0.465 | ambiguous | 0.4473 | ambiguous | -1.201 | Destabilizing | 0.944 | D | 0.579 | neutral | None | None | None | None | N |
| I/R | 0.3399 | likely_benign | 0.3119 | benign | -0.853 | Destabilizing | 0.893 | D | 0.603 | neutral | None | None | None | None | N |
| I/S | 0.2892 | likely_benign | 0.2649 | benign | -2.03 | Highly Destabilizing | 0.27 | N | 0.435 | neutral | N | 0.445503983 | None | None | N |
| I/T | 0.1187 | likely_benign | 0.1119 | benign | -1.771 | Destabilizing | 0.425 | N | 0.419 | neutral | N | 0.431073248 | None | None | N |
| I/V | 0.0862 | likely_benign | 0.088 | benign | -1.093 | Destabilizing | 0.244 | N | 0.319 | neutral | N | 0.413444705 | None | None | N |
| I/W | 0.6458 | likely_pathogenic | 0.6043 | pathogenic | -1.2 | Destabilizing | 0.995 | D | 0.585 | neutral | None | None | None | None | N |
| I/Y | 0.3715 | ambiguous | 0.349 | ambiguous | -0.945 | Destabilizing | 0.543 | D | 0.48 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.